Major blood loss secondary to upper gastrointestinal bleeding occurs in only a small percentage of patients with sepsis. However, minor blood loss within 24 h of developing a severe infection is common as patients develop painless 1- to 2-mm erosions in the mucosal layer of the stomach and/or duodenum. Proposed mechanisms for these ulcerations include decrease in the blood flow, hypoxia of the mucosal cells, interruption of the gastric mucosal barrier, and release of mucosal lysozyme.
The most frequent hematologic changes in the septic patient are neutropenia or neutrophilia, thrombocytopenia, and disseminated intravascular coagulation (DIC). Sepsis most frequently produces a neutrophilic leukocytosis with a "left shift." These early changes result from demargination and release of less-mature granulocytes from the marrow storage pools. One proposed mechanism for demargination and bone marrow release is the presence of endotoxin or other similar substances and activation by complement (C3a) causing the release of a neutrophil-releasing substance. The sustained neutrophilia that accompanies chronic infection is thought to be secondary to colony stimulating factors. These glycoproteins increase granulocyte production by activating committed stem cells. Infection increases the colony-stimulating factor elaboration by macrophages, lymphocytes, and other tissues. In certain cases of sepsis, leukemoid reactions with leukocyte counts of 50,000 to 100,000 cells/pL have been reported.
Neutropenia, occurring rarely, is associated with an increase in mortality. The etiology of this neutropenia includes increased peripheral utilization of neutrophils, damage to neutrophils by bacterial byproducts, or depression of marrow granulocyte production by inflammatory mediators. Both morphologic and functional changes to neutrophils have been reported in sepsis. The most commonly reported morphologic changes include the presence of toxic granulations, Dohle bodies, and vacuolization. Functional changes reported in sepsis include increased phagocytic and cytotoxic activities. Eosinophilia occurring in the presence of sepsis has been attributed to the effect of margination or migration of these cells from the vascular space, inhibition of bone marrow release, and a decrease in marrow production. Activated complement C5a has been implicated.
Red cell number and morphologic characteristics are not usually affected by sepsis. However, red cell production and survival are decreased during sepsis. Decreased production and survival do not usually cause anemia unless the infection is prolonged. Septic patients generally possess low serum iron concentrations. Sepsis and its intermediaries cause a rapid iron flux into the liver and other parts of the reticuloendothelial cells, with the serum iron concentration decreasing by 50 percent or more within a period of hours. This effect may last days. An attractive hypothesis is that this represents a host defense mechanism. The addition of iron to normal human serum enhances the growth of organisms. Also, iron in the reticuloendothelial system may be beneficial to the host cells in detoxifying bacterial activity.
Thrombocytopenia most frequently arises as a consequence of DIC, although isolated thrombocytopenia is present in over 30 percent of cases of sepsis. Thrombocytopenia may be an early clue to bacteremia and may also be useful in observing patient's response to therapy. The proposed mechanisms for the thrombocytopenia include inhibition of thrombopoiesis, increased platelet turnover, increased endothelial adherence, and increased destruction secondary to immunologic mechanisms.
DIC is a condition in which the clotting and/or fibrinolytic system are systemically activated, leading to the consumption of many coagulation factors and platelets. DIC, with disseminated fibrin depositions in the microcirculation of various organ systems, is a frequent finding in patients with septic shock. The activation of the hemostatic (clotting) system is due primarily to the activation of the extrinsic pathway of clotting. This cascade is triggered by multiple sources including bacteria
(gram-negative and gram-positive), viruses, fungi, endotoxins, and exotoxins (see Fig 28-2). Gram-negative infections precipitate DIC more readily than does gram-positive bacteremia. The fibrinolytic system is also activated in sepsis and plays an important role in the regulation of fibrin deposition in the microcirculation. Several studies of septic patients have demonstrated the release of tissue type plasminogen activator, which activates the fibrinolytic system, at least initially in sepsis. As sepsis progresses, there is an increased release of plasminogen activator inhibitor type 1 (PAI-1), which blocks plasmin generation and thus contributes to fibrin deposition in the microcirculation and subsequent multiple-organ failure.
DIC can be categorized into two forms. The compensated form of DIC is characterized by a "slower" generalized activation of the hemostatic system. Although platelets and coagulation factors are consumed more rapidly than normal, bleeding is prevented by increasing coagulation factor production in the liver, by the release of the platelets from reserve storage sites, and by the synthesis of inhibitors at an accelerated rate. Patients with decompensated DIC will have clinical bleeding and/or thrombosis. Laboratory studies suggesting the presence of DIC include thrombocytopenia, prolonged prothrombin and activated partial thromboplastin values, decreased fibrinogen and antithrombin III levels, and increased fibrin monomer, fibrin split products, and D-dimer values.
Was this article helpful?
Awesome Ways To Get Over Your Mentality That Keeps you Overweight! This Book Is One Of The Most Valuable Resources In The World When It Comes To Results In Your Slim-down and Health Efforts! Day in day out we keep ourselves absorbed with those matters that matter the most to us. A lot of times, it might be just to survive and bring in some money. In doing so we at times disregard or forget about the extra matters that are essential to balance our lives. They’re even more essential to supply real meaning to our world. You have to pay attention to your wellness.